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.

The outcome of physical symptoms with treatment of depression.

OBJECTIVE: This study examined the prevalence, impact on health-related quality of life (HRQoL), and outcome of physical symptoms in depressed patients during 9 months of antidepressant therapy. DESIGN: Open-label, randomized, intention-to-treat trial with enrollment occurring April through November 1999. SETTING: Thirty-seven primary care clinics within a research network. PATIENTS: Five hundred seventy-three depressed patients started on one of three selective serotonin reuptake inhibitors (SSRIs) by their primary care physician and who completed a baseline interview. INTERVENTIONS: Patients were randomized to receive fluoxetine, paroxetine, or sertraline. MEASUREMENTS AND MAIN RESULTS: Outcomes assessed included physical symptoms, depression, and multiple domains of HRQoL. Prevalence of physical symptoms was determined at baseline and after 1, 3, 6, and 9 months of treatment. Stepwise linear regression models were used to determine the independent effects of physical symptoms and depression on HRQoL domains. Of the 14 physical symptoms assessed, 13 were present in at least a third to half of the patients at baseline. Each symptom showed the greatest improvement during the initial month of treatment. In contrast, depression continued to show gradual improvement over a 9-month period. Physical symptoms had a predominant effect on pain (explaining 17% to 18% of the variance), physical functioning (13%), and overall health perceptions (13% to 15%). Depression had the greatest impact on mental (26% to 45%), social (14% to 32%), and work functioning (9% to 32%). CONCLUSIONS: Physical symptoms are prevalent in depressed patients and initially improve in the first month of SSRI treatment. Unlike depression, however, improvement in physical symptoms typically plateaus with minimal resolution in subsequent months.