Dehydroepiandrosterone and cortisol as markers of HPA axis dysregulation in women with low sexual desire

Previous research has found lower serum levels of dehydroepiandrosterone (DHEA) or its sulfated form, DHEA-S, in women diagnosed with Hypoactive Sexual Desire Disorder (HSDD). Given that DHEA and DHEA-S have multiple direct actions on the brain as well as anti-glucocorticoid properties, it is possible that lower levels of DHEA directly impact women’s sexual functioning. To date, the significance of the lower DHEA levels remains unclear. To our knowledge, there has been no empirical study of stress hormones as markers of HPA dysregulation in women with HSDD. To attend to this gap, the present study utilized several measures of HPA axis function – morning and evening cortisol and DHEA, the cortisol awakening response (CAR), diurnal cortisol slope, and cortisol:DHEA ratio – and examined their relationship with sexual functioning in N = 275 women with (n = 137) and without (n = 138) HSDD. Results demonstrated multiple hormonal markers of HPA dysregulation in women diagnosed with HSDD compared to control participants, specifically, lower AM cortisol and DHEA levels, a flatter diurnal cortisol slope, and a lower CAR. Overall, results of the present study indicate that persistently low sexual desire in women is associated with HPA axis dysregulation, with both cortisol and DHEA alterations potentially detrimental to sexual desire.Medicine, Faculty ofNon UBCCellular and Physiological Sciences, Department ofObstetrics and Gynaecology, Department ofPsychiatry, Department ofReviewedFacultyPostdoctoralGraduat

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921