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. 2019 Jun 1;8(6):672-679.
doi: 10.1530/EC-19-0110.

Validity of free testosterone calculation in pregnant women

M P Schuijt  1   2 , C G J Sweep  2 , R van der Steen  2 , A J Olthaar  2 , N M M L Stikkelbroeck  3 , H A Ross  2 , A E van Herwaarden  2
Affiliations

Validity of free testosterone calculation in pregnant women

M P Schuijt et al. Endocr Connect. .

Abstract

Objective Increased maternal testosterone concentration during pregnancy may affect the fetus. Therefore it is clinically relevant to have a quick and reliable method to determine free testosterone levels. Current calculators for free testosterone are suspected to perform poorly during pregnancy due to suggested competition between high levels of estradiol and free (bio-active) testosterone for sex hormone-binding globulin (SHBG) binding. Therefore, it is claimed that reliable calculation of free testosterone concentration is not possible. However, recent evidence on SHBG-binding sites questions the estradiol effect on the testosterone-SHBG binding during pregnancy. In this study, we investigated whether the free testosterone concentration can be calculated in pregnant women. Design and methods Free testosterone was measured with a specially developed equilibrium dialysis method combined with liquid chromatography tandem mass spectrometry (LC-MS/MS). Free testosterone was also calculated with the formulas of Vermeulen et al. and Ross et al. Results Total and free testosterone measured in healthy men and women were in good agreement with earlier reports. In pregnant women, total testosterone values were higher than in non-pregnant women, whereas free testosterone values were comparable. Calculated free testosterone levels in pregnant women were highly correlated, but marginally higher, compared to measured free testosterone levels. Conclusions We developed an equilibrium dialysis-LC-MS/MS method for the measurement of free testosterone in the low range of pregnant and non-pregnant women. Although during pregnancy total testosterone is increased, this is not the case for free testosterone. The free testosterone formulas perform well in pregnant women.

Keywords: calculation; estradiol; free testosterone; pregnancy; woman.

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Figures

Figure 1
Figure 1
Chromatogram of free testosterone in a sample of 1 pmol/L (i.e. LC-MS/MS measurement in a concentrated solid phase extracted dialysate of 5 pmol/L).
Figure 2
Figure 2
Free testosterone levels in men and women at different ages.
Figure 3
Figure 3
Total testosterone and free testosterone levels in pregnant women (12 and 27 weeks of gestation) and non-pregnant women.
Figure 4
Figure 4
Free testosterone and estradiol levels in women at 12 and 27 weeks of gestation, arranged per individual in order of increasing estradiol. Free testosterone levels are measured with ED-LCMS/MS (green), calculated with the free testosterone formula of Ross et al. (blue) and the formula of Vermeulen et al. (red). Estradiol levels are shown as gray bars.
See this image and copyright information in PMC

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