Changes in serum levels of SHBG, endogenous ligands and levonorgestrel induced by ethinylestradiol in NORPLANT^R users

This work was done in search for a model to examine target organ response to fluctuations in serum levels of sex hormone-binding globulin (SHBG) and its ligands. The time course and magnitude of fluctuations of SHBG, levonorgestrel (L-Ng), estradiol (E₂), testosterone (T) and dihydrotestosterone (DHT) in serum were examined during and after treatment with 50 ug of ethinylestradiol (EE₂) daily for 10 days in 10 volunteer women using NORPLANT^R implants. Six of these volunteers were also treated with 20 ug of EE₂ daily for 7 days and two additional volunteers using a copper-T IUD were treated with 50 ug of EE₂ daily for 7 days. In all cases, SHBG and L-Ng levels increased in a close parallel manner several-fold above basal levels during treatment, reaching a maximum around two days after the last EE₂ pill. In contrast, the levels of E₂ and T increased in one subject, decreased in 5 and remained unchanged in 4, while changes of DHT were unrelated to those of the other ligands. Since the L-Ng "secretion rate" by NORPLANT^R implants is constant, it follows that the effect of EE₂ on its levels is due to a decreased metabolic clearance rate, most likely secondary to the increased binding of L-Ng to SHBG in serum. This interpretation is in agreement with the close parallelism in the fluctuations of L-Ng and SHBG.