Effect of two oral contraceptives containing ethinylestradiol and gestodene or norgestimate upon androgen parameters and serum binding proteins

Abstract

The effect of a triphasic oral contraceptive containing ethinylestradiol and gestodene (EE/GSD) on various serum hormonal parameters was compared with that of a monophasic formulation containing 35 micrograms ethinylestradiol and 250 micrograms norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth and twelfth treatment cycle. There was no significant difference in the influence on any hormonal parameter between both formulations. Both EE/GSD and EE/NGM caused a time-dependent suppression of serum dehydroepiandrosterone sulphate (DHEA-S) by 20-30% (p < 0.01) and a reduction of 5 alpha-androstane-3 alpha, 17 beta-diol glucuronide by 50-60% (p < 0.01) during each treatment cycle, while androstenedione levels were reduced by 25% (p < 0.01). There was also a significant decrease in the levels of total testosterone by 30-35% (p < 0.01) and free testosterone by 60% (p < 0.01), while sex hormone-binding globulin (SHBG) was increased by 200-240% on days 11 and 21 (p < 0.01). During the pill-free interval the SHBG levels were reduced to a certain degree but remained elevated by 100% as compared to the pretreatment values. The serum levels of corticosteroid-binding globulin (CBG) which is known to be influenced only by the estrogenic component of combination pills, increased significantly by 170% (p < 0.01) during each treatment cycle. During the pill-free interval of 7 days, the CBG levels decreased but were still elevated by 90-100% as compared to the control cycle. Similarly, the serum levels of cortisol were significantly elevated by 110-140% (p < 0.01) during treatment with both preparations. The results demonstrate a profound suppression of androgen levels and peripheral androgen metabolism.

PIP: At the J. W. Goethe University Hospital in Frankfurt am Main, Germany, researchers randomly allocated 46 women to use either the triphasic oral contraceptive (OC) containing 30 mcg ethinyl estradiol (EE) and 50 mcg gestodene or the monophasic OC containing 35 mcg EE and 250 mcg norgestimate. They wanted to compare the effects of the two OCs on different serum hormonal parameters and serum binding proteins. Health workers took blood samples from the women on days 2, 11, and 21 of the cycle before OC use and of treatment cycles 3, 6, and 12. The two groups had similar hormonal parameters. Both OCs suppressed serum levels of dehydroepiandrosterone sulphate (DHEA-S) by 20-30% (p 0.01). They reduced 5alpha-androstane-3alpha, 17beta-diol glucuronide by 50-60% (p 0.01) during each treatment cycle. Both OCs also reduced androstenedione serum levels by 25% (p 0.01). Both OCs reduced serum levels of total testosterone by about 30% and of free testosterone by 60% (p 0.01-0.05 and p 0.01, respectively). The 200% increase of serum levels of sex hormone binding globulin (SHBG) on days 11 and 21 of each cycle in both groups (p 0.01) caused the more pronounced decrease of serum levels of free testosterone. Suppression of ovarian androgen synthesis also contributed to the more pronounced decrease of free testosterone. SHBG levels fell during the pill-free interval but remained 100% higher than pretreatment values. Serum levels of corticosteroid binding globulin (CBG) increased by 170% during each treatment cycle (p 0.01). CBG levels fell during the pill-free interval, but remained higher by 90-100% than the pretreatment cycle. Only the estrogenic component affected the increase in CBG. Both OCs increased cortisol serum levels by 110-140% (p 0.01). These findings show that both OCs significantly suppressed some androgen parameters and peripheral androgen metabolism.