Original research article| Volume 76, ISSUE 1, P8-17, July 2007

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 ��g of ethinyl estradiol

  • Teri Greco
    Department of Medicine, Regenstrief Institute for Health Care, Indiana University School of Medicine, Indianapolis, IN 40202, USA

    Department of Medicine, Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
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  • Cynthia A. Graham
    Corresponding author. Oxford Doctoral Course in Clinical Psychology, Isis Education Centre, Warneford Hospital, Headington, Oxford OX3 7JX, UK. Tel.: +44 1865 226431; fax: +44 1865 226364.
    Oxford Doctoral Course in Clinical Psychology, Isis Education Centre, Warneford Hospital, OX3 7JX Oxford, UK

    The Kinsey Institute for Research in Sex, Gender, and Reproduction, Indiana University, Bloomington, IN 47405-2501, USA
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  • John Bancroft
    The Kinsey Institute for Research in Sex, Gender, and Reproduction, Indiana University, Bloomington, IN 47405-2501, USA
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  • Amanda Tanner
    Department of Applied Health Science, Indiana University, Bloomington, IN 47405-7109, USA
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  • Helen A. Doll
    Department of Public Health, University of Oxford, OX3 7LF Oxford, UK
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      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 ��g EE ��� in their effects on androgens, mood and sexual interest in women starting on OCs.


      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.


      Sixty women, all university students, were randomized to receive either the 25 ��g EE (N/EE25) or the 35 ��g 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 ��mol/L); N/EE25: from 7.50 to 5.39 ��mol/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).


      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.


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