The effects of oral contraceptives on androgen levels and their relevance to premenstrual mood and sexual interest: a comparison of two triphasic formulations containing norgestimate and either 35 or 25 microg of ethinyl estradiol.

Purpose: This study compared two oral contraceptives (OCs) with the same triphasic regimen of progestin (norgestimate 0.18, 0.215 and 0.25 mg) but differing doses of ethinyl estradiol (EE) - 25 and 35 microg EE - in their effects on androgens, mood and sexual interest in women starting on OCs.

Methods: Total testosterone (T), free testosterone (FT), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-S), together with measures of mood [Beck Depression Inventory (BDI)], sexual interest [Dyadic and Solitary subscales of the Sexual Desire Inventory (SDI)] and self-reported side effects were assessed before starting on the OC and again after 3 months of use.

Results: Sixty women, all university students, were randomized to receive either the 25 microg EE (N/EE25) or the 35 microg EE (N/EE35) pill; 12 women discontinued, leaving 48 who completed the 3-month study. Their mean age was 19.7 years (18-30) and they were predominantly white and single. Both OCs produced reductions in mean T [N/EE35: from 1.33 to 0.60 nmol/L, p<.001; N/EE25: from 1.12 to 1.02 nmol/L; nonsignificant (NS)] and FT (N/EE35: from 41.3 to 4.4 pmol/L, p<.001; N/EE25: from 25.4 to 7.9 pmol/L, p<.01), but the reduction in both T and FT was significantly greater with the higher EE dose (N/EE35) (p=.05 and p=.03, respectively). DHEA-S was also reduced with both formulations (N/EE35: from 7.26 to 5.22 micromol/L); N/EE25: from 7.50 to 5.39 micromol/L), although the reduction was only significant in the N/EE35 group (p<.02). Considerable variability in changes in mood was evident with both OCs, with some women showing predominantly negative effects (10 in N/EE35, 5 in N/EE25); others, positive effects (9 in N/EE35, 17 in N/EE25) and some, no change (four in each group). Women using N/EE25 were significantly more likely to show improvement in premenstrual mood than those in the N/EE35 group (p<.02), although there was no correlation between changes in BDI and FT or DHEA-S. Sexual interest scores did not change significantly from baseline to posttreatment with either OC (N/EE35: dyadic, from 40.5 to 39.6, NS; solitary, from 5.9 to 6.4, NS; N/EE25: dyadic, from 36.7 to 37.0, NS; solitary, from 5.0 to 4.2, NS).

Conclusion: The lower EE pill reduced FT less and was associated with greater improvement in premenstrual mood. A causal relation between these two effects is uncertain.