Pregnancy-Induced Perturbation of Urinary Androgenic Steroid Disposition

Abstract

ObjectiveTo investigate the excretion and conjugation profile of testosterone (T), Epitestosterone (EpiT), and other androgen metabolites in different phases of pregnancy and postpregnancy as a reflection of the “androgenic exposure.”DesignConsecutive recruitment of pregnant women.SettingMaternity outpatient low-risk pregnancy clinic.PatientsSeventy-seven pregnant women.InterventionsCollection of urine for analyses of sulfate (S) and glucuronide (G) conjugates and metabolic ratios of androgens and androgen metabolites using liquid chromatography-tandem mass spectrometry.Main Outcome MeasuresExcretion profiles and metabolic ratios of G and S conjugates of T, EpiT, dehydroepiandrosterone (DHEA), androsterone (A), etiocholanolone (Etio), and dihydrotestosterone in relation to trimester and postpartum, body mass index, fetal sex, and ethnicity.ResultsT-S excretion increased significantly between the second and third trimester, whereas excretion of T-G did not change. In contrast, both conjugates of EpiT increased markedly, more so for the S-(17-fold) than the G-conjugate (1.6-fold). The preference for S over G conjugation was conspicuous for EpiT and DHEA (S/G ratio 2.1 and 4.7, respectively, in the third trimester), whereas the reverse was true for T, A, and Etio (S/G 0.6, 0.13, and 0.11, respectively).ConclusionsPregnancy influences the androgen excretion profile, with the most profound change being an increase in EpiT excretion throughout the trimesters. EpiT may modulate the effect of T, but its exact role during pregnancy is not known. There were marked differences in the S/G conjugate ratios between androgens upstream and downstream from T in the metabolic network. These results are interesting to compare with the androgen disposition in women with endocrine disorders or abuse of steroids.

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“…Challengingly, hormonal contraceptives and levonorgestrel emergency contraception have been demonstrated to lower epitestosterone lev-els, which may result in AAFs [33,34]. Conversely, epitestosterone increases throughout pregnancy; this change could further complicate ABP interpretation [35]. A similar strategy compares the 13 C: 12 C carbon isotope ratio of samples, to assess for known differences in synthetic versus endogenous steroids [32].…”