Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA)

source extracted confidence: high 2026-04-09
#biological-availability #chromatography-liquid #contraceptives-oral-combined #dehydroepiandrosterone #female

Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA)

Heijboer et al., 2014 | Clin Chim Acta | Rct

Citation

Heijboer Annemieke C, Zimmerman Yvette, ... Blankenstein Marinus A. Peculiar observations in measuring testosterone in women treated with oral contraceptives supplemented with dehydroepiandrosterone (DHEA). Clin Chim Acta. 2014-Mar-20;430:92-5. doi:10.1016/j.cca.2013.12.042

Abstract

Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC-MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC-MSMS method. This method was compared to another LC-MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC-MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n = 198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r = -0.676; p<0.001). By contrast, testosterone results obtained by LC-MSMS were not related to SHBG (r = 0.100; NS). In conclusion, our results indicate that total testosterone measurements during oral contraceptive use are unreliable when performed with assays sensitive to the SHBG concentration. The discrepancy with the literature can most likely be explained by the sensitivity of the immunoassay used to SHBG. Given the sharp increase in SHBG during the use of many oral contraceptives, total testosterone may not decrease, whereas its bioavailability, estimated by free testosterone levels, will be diminished. Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account.

Key Findings

Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 198
Age Range See abstract
Condition See abstract

MeSH Terms

  • Biological Availability
  • Chromatography, Liquid
  • Contraceptives, Oral, Combined
  • Dehydroepiandrosterone
  • Female
  • Humans
  • Radioimmunoassay
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sex Hormone-Binding Globulin
  • Tandem Mass Spectrometry
  • Testosterone
  • Uncertainty

Evidence Classification

  • Level: Rct
  • Publication Types: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial
  • Vertical: DHEA-hormonal

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09