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Tuesday, July 28, 2015

Birth Control ... Do We Know The Full Story?

Oral contraceptives (OCs) affect the concentrations of steroid metabolites by eliciting a decrease in the adrenal and ovarian androgen synthesis and an increase in the hepatic production of sex hormone-binding globulin (SHBG) (for review see Zimmerman et al. [4]). Thus, information of OC use is vital in interpreting data on circulating steroid metabolites in females.
We found that OC users had significantly lower concentrations of all steroid metabolites as well as of fT and FAI. The markedly lower levels observed for fT and FAI are most likely caused by high SHGB concentrations in OC users compared to controls. OCs decrease ovarian steroidogenesis by inhibition of gonadotropins. In addition, the marked effects in the present study of OCs on DHEA, DHEAS, 17-OHP, Adione and T suggest direct effects of OCs on adrenal steroid production. This is in line with previous studies: significantly lower circulating concentrations of 17-OHP, T and Adione were reported in women with polycystic ovarian disease-related hyperandrogenism after treatment with OCs containing ethinyl estradiol (EE) and the anti-androgen cyproterone acetate as compared to baseline values [26]. Likewise, OCs containing 17β-estradiol in combination with the anti-androgen nomegestrol were reported to cause significant reductions in circulating levels of DHEAS, Adione, T and fT and were found to increase SHBG concentrations in healthy women [27]. OCs containing EE in combination with gestodene or levonorgestrel (both having relatively neutral androgenic effects) were also found to significantly lower circulating concentrations of DHEAS, Adione and T and to increase SHBG in healthy women [27] and [28], whereas EE in combination with the anti-androgen drospirone was found to significantly reduce circulating concentrations of T and fT, but not of DHEAS, Adione and 17-OHP in women with polycystic ovary syndrome [29]. In this latter study significant effects of OCs on 17,20-lyase activity were reported, which is in accordance with finding in the current study (data not shown). More specific studies are needed to further elucidate the potential effects of OCs on enzymatic activity. We do not have detailed information on the type of OCs used by our participants and therefore cannot further evaluate the effects of different gestagens on adrenal androgen secretion based on our data. None of the studies of OCs referred to above used mass spectrometry-based methods for the analysis of the steroid metabolites. With low levels of steroid metabolites in women – and typically even lower concentrations after treatment with OCs – the use of mass spectrometry-based methods for future studies on this subject must be highly recommended.
In conclusion, we have established serum reference ranges from 3 months to 25 and 20 years of age for males and females, respectively, for selected steroid metabolites, the ratios between them, fT and FAI. The steroid levels were strongly associated with sex, age and pubertal development. Furthermore, the LC–MS/MS-based method allows for quantitative information about ratios between the steroid metabolites, which may assist in the diagnosis of specific disorders of steroid biosynthesis. Finally, use of oral contraceptives strongly influences adrenal steroidogenesis and should be considered when diagnosing and monitoring treatment of patients with DSD.


Another related study ...


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