However , subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences : COCs containing second generation progestins and /or the lower estrogen doses ( 20–25 µg EE ) were found to have less impact on SHBG concentrations .
The current literature review and meta- analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations .
Due to the SHBG increase , free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T , but both affect SHBG .
BACKGROUND Combined oral contraceptives ( COCs ) reduce levels of and rogen , especially testosterone ( T ) , by inhibiting ovarian and adrenal and rogen synthesis and by increasing levels of sex hormone-binding globulin ( SHBG ) .
Although this suppressive effect has been investigated by numerous studies over many years , to our knowledge no systematic review concerning this issue had been performed .
Pharmacokinetics of levonorgestrel and ethinylestradiol in 14 women during three months of treatment with a tri-step combination oral contraceptive: serum protein binding of levonorgestrel and influence of treatment on free and total testosterone levels in the serum.
The pharmacokinetics of levonorgestrel ( LNG ) and ethinylestradiol ( EE2 ) were determined in 14 healthy women ( age 18 to 27 years ) during a treatment period of three months with a tri-step combination oral contraceptive ( Triquilar ) .  Prior to this treatment period , the same women received a single administration of a coated tablet containing 0.125 mg LNG together with 0.03 mg EE2 . There was a washout phase of one week between both treatments . Following single dose administration , a mean terminal half-life of 22 h was observed for LNG . The total clearance was 1.0 ml x min-1 x kg-1 and the volume of distribution was 128 l. During a treatment cycle , LNG levels in the serum accumulated by a factor of about four as compared to single dose administration . Steady-state drug levels were reached during the second half of each cycle . As compared to single dose administration , the following changes were observed for LNG at the end of treatment cycles one and three : reduced total ( 0.5 ml x min-1 x kg-1 ) and free clearance ( 50 ml x min-1 x kg-1 ) and a reduced volume of distribution ( 52 l ) . A concomitant increase in the SHBG concentrations by a factor of two as compared to pretreatment values was observed during treatment and appeared to be mainly responsible for the changes in the pharmacokinetics of LNG . Marked changes were also seen for the serum protein binding of LNG . After single dose administration , the free fraction of LNG was 1.4 % and the fractions bound to SHBG and albumin were 55.0 % and 43.6 % , respectively . At the end of cycle one , the free fraction was only 1.0 % and the fractions bound to SHBG and albumin were 69.4 % and 30.0 % , respectively . There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of LNG at the end of cycles one and three . On the last day of treatment cycles one and three , the AUC(0 - 4h ) values of EE2  were 331.2 and 369.6 pg x ml-1 x h , respectively , which corresponds to an about 11 - 24 % increase as compared to single dose administration , where an AUC(0 - 4h ) value of 298.3 pg x ml-1 x h was found . Total and free testosterone concentrations decreased during treatment cycles one and three by about 41 % and 55 % , respectively , compared with the corresponding values measured prior to treatment
However , subgroup analyses for the estrogen dose and the progestin type in relation to changes in SHBG levels did show significant differences : COCs containing second generation progestins and /or the lower estrogen doses ( 20–25 µg EE ) were found to have less impact on SHBG concentrations .
The current literature review and meta- analysis demonstrates that COCs decrease circulating levels of total T and free T and increase SBHG concentrations .
Due to the SHBG increase , free T levels decrease twice as much as total T. The estrogen dose and progestin type of the COC do not influence the decline of total and free T , but both affect SHBG .
BACKGROUND Combined oral contraceptives ( COCs ) reduce levels of and rogen , especially testosterone ( T ) , by inhibiting ovarian and adrenal and rogen synthesis and by increasing levels of sex hormone-binding globulin ( SHBG ) .
Although this suppressive effect has been investigated by numerous studies over many years , to our knowledge no systematic review concerning this issue had been performed .