Effects of Oral Contraceptive on Thyroid Hormones and Androgen Paramenters: Conventional VS. Extended cycle

1. Effects of Oral Contraceptive on Thyroid Hormones and Androgen Paramenters: Conventional VS. Extended cycle

2. A Little Bit of Background OCs influnence the H-P-O Axis and reduce the ovarian production of sex steroids but also affect (directly or indirectly) other endocrine systems Adrenal Fcn Thyroid Fcn 2 main components of OCs Estrogen component = ethinyl estradiol (EE) Causes a dose-dependent rise in the serum concentration of sex hormone-binding globulin (SHGB) and thyroxine-binding globulin (TBG) SHGB- acts as a binder to testosterone and estradiol that circulate within the bloodstream, only allowing a few free hormones of T and E2 to ester the cell and activate its receptor (biologically active) TBG- responsible for carrying the thyroid hormones T3 and T4 into the bloodstream Progestin component (with androgenic activity0 May counteract this estrogenic effect A rise in SHBG leads to enhanced protein binding of circulating testosterone resulting in reduction of free, biologically active testosterone by 40-60% Limited effect bc an eccessive elevation of SHGB conc is associated with attenuation of its specific binding capacity Rise in TBG results in a reduced clearance of T4 and T4, thus creating an increase in total T3 and T4 by 20-40%

3. OCs with progestins without androgenic properties like DNG. . . Rise in SHGB levels by 200-300% Rise in TGB levels by 50-60% Changes noted above are partly reversed in hormone-free interval of 7 days Max levels of SHGB are reached at end of 3rd cycle, with no further rise during subsequent cycles The fluctuations of hormones during conventional treatment with OCS may cause menses-related disorders and hormone withdrawal symptoms, many women prefer to use extended cycle method Still unclarified whether or not continuous daily use of Ocs (12 weeks) represent a more pronounced impact on various endocrine and metabolic systems than conventional use

4. The Study Investigating the effects of an OC, specifically containing 30mcg ethinyl estradiol (EE) and 2mg dienogest (DNG) [EE/DNG] on. . . . Thyroid Hormones Androgen parameters Group of 59 women at Center of Obstetrics and Gyecology, University Hospital of Frankfurt Note: chosen subgroup within the frame of a large multicenter, comparative, prospective, randomized , 12 mo efficacy and safety study Chosen by regular menstral cycles, screened for obesity (since birth control may have different effects for heavier set people), PTSD, thyroid issues No hormonal meds use 4 weeks prior to sudy and did not use any drugs known to influence effects of OCs General, Gyenocological exams carried out before, during study, and 28 days after termination of treatment 1 control cycle Monitored serum concentration of androgens, SHGB, TBG and thyroid hormones for. . . Extended cycle (84+7 days) -> (4 extendede cycles with 84 days of continuous administration + 7 days without hormones) Conventional Cycle (21+7 days) -> 13 cycles with 21 days of treatment + 7 days without hormones) Time Posts were 3 and 12 months Blood taken on days 21-26 of the control cycle Blood taken on days 82-84 of 1st and 4th extended cycles {3 & 12 mos respectively) Blood taken on days 19-21 of 3rd and 13th cycle {3 & 12 mos respectively} NOTE: Blood taken in morning, lying down and fasting, each volunteer kept cycle diary for tablet intake and bleeding events

5. Lab Portion Methods Blood samples centrifuged and sera stored at -80* until analysis. Total T3 and T4, free T3 and free T4, and Total T and free T determined by direct solid-phase chemiluminescent immunoassay TGB determined by radio-immunoassay SHGB by an immuno-radiometric assay

6. Results Thyroid hormones Rise in serum levens of TGB (60-65% con, 70% extended) Total T3 incr significantly by 35% for both regimes fT3 showed no significant changes Total T4 incr also in both regimes by 35-40% fT4 showen no significant changes SHGB & Androgen Paramenters EC and Con rise of SHGB by 210-203% by 3 months and only enhanced a bit after 12months by 220-250% Total testonsterone for both regimes had a significant reduction by about 40% after 3 months, which the values remained stable until 12 months Free testosterone levels profoundly suppressed by 55-65% after 3 and 12 months