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.
OBJECTIVE
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).


CONCLUSIONS
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.
Greco
Teri
T
Department of Medicine, Regenstrief Institute for Health Care, Indiana University School of Medicine, Indianapolis, IN 40202, USA.
Graham
Cynthia A
CA
Bancroft
John
J
Tanner
Amanda
A
Doll
Helen A
HA
D000293:Adolescent; D000328:Adult; D000339:Affect / Q000187:drug effects*; D000728:Androgens / Q000097:blood*; D003277:Contraceptives, Oral, Combined / Q000008:administration & dosage*; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004997:Ethinyl Estradiol / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D009644:Norgestrel / Q000008:administration & dosage / Q000031:analogs & derivatives*; D011293:Premenstrual Syndrome; D012738:Sex Hormone-Binding Globulin / Q000187:drug effects; D012725:Sexual Behavior / Q000187:drug effects; D011795:Surveys and Questionnaires; D013739:Testosterone / Q000097:blood; D016896:Treatment Outcome
D000728:Androgens; D003277:Contraceptives, Oral, Combined; D012738:Sex Hormone-Binding Globulin; D009644:Norgestrel; D013739:Testosterone; D004997:Ethinyl Estradiol; D019314:Dehydroepiandrosterone Sulfate; C017576:norgestimate