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 .
Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol.
The pharmacokinetics and and rogenic activity of Estrostep , a new oral contraceptive providing low-dose estrogen in a graduated sequence with a constant dose of progestin , were characterized in an open-label , nonr and omized study in 17 normally cycling women treated for three cycles with Estrostep .  Women received 1 mg of norethindrone acetate daily combined with 20 microg of ethinyl estradiol daily for the first 5 days ( 1/20 ) , 30 microg of ethinyl estradiol daily for the next 7 days ( 1/30 ) , and 35 microg of ethinyl estradiol daily for 9 days ( 1/35 ) . No medication was given for 7 days in each cycle to allow for withdrawal bleeding . Serial blood sample s for the measurement of ethinyl estradiol and norethindrone concentrations were collected on days 5 , 12 , and 21 of the third treatment cycle for the 1/20 , 1/30 , and 1/35 dose , respectively . Sex hormone-binding globulin ( SHBG ) and free testosterone were measured at baseline , on day 1 of cycles 2 and 3 ( SHBG only ) , and on days 5 , 12 , and 21 of cycle 3 . Mean steady-state plasma ethinyl estradiol and norethindrone concentrations increased over cycle 3 . The increases in ethinyl estradiol concentrations were proportional to dose . The increases in norethindrone concentrations were related to ethinyl estradiol-dependent increases in SHBG concentrations , which were 218 % , 253 % , and 296 % of baseline values on days 5 , 12 , and 21 , respectively . Mean plasma free testosterone concentrations decreased 47 % , 60 % , and 64 % below baseline on days 5 , 12 , and 21 of cycle 3 , respectively . Graduated ethinyl estradiol doses combined with a constant norethindrone acetate dose progressively increase SHBG and decrease free testosterone , which overrides any theoretic concerns of and rogenic activity of norethindrone acetate . Although true and rogenic activity can be determined only by assessing endpoints such as acne , hirsutism , and lipids in large controlled trials , the observed changes in circulating SHBG and free testosterone concentrations indicate that Estrostep has little , if any , intrinsic and rogenic activity
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 .