104 Flibanserin Subset Analyses and the Androgenics of Hypoactive Sexual Desire Disorder

Abstract

The success rate with flibanserin (FLI) in treating premenopausal women with Hypoactive Sexual Desire Disorder (HSDD) was about 50% in clinical trials. No subsets of subjects more or less responsive in clinical trials of efficacy were identified by regulatory authorities or the drug’s sponsors. Now that other treatments are becoming available, identifying baseline characteristics of patients more or less likely to respond could improve rational selection of treatments for HSDD. Determine whether the available clinical research data on flibanserin to treat HSDD have established or suggested baseline characteristics associated with higher or lower response rates to FLI. Explore whether the findings can be extrapolated to other treatments for HSDD. Review subset data in the available summary documents on flibanserin, preferably seeking conclusions but at least identifying coherences. Review androgen literature relevant to HSDD. Six detailed reviews of the efficacy study Results of FLI were found. Each document recommends against the safety of use by women taking certain concomitant medications or alcohol, but none concludes that any baseline factor predicts efficacy or inefficacy. Analyses of baseline variables in the first review, however, showed that normal sex hormone plasma levels were associated with superiority numerically exceeding that in the overall study population. Non-significant efficacy vs placebo was associated with abnormally low testosterone (T) or dehydroepiandrosterone sulfate (DHEAS), high sex hormone binding globulin (SHBG), and especially with hormonal contraceptive (HC) use. HC use was also associated with higher plasma FLI levels and more frequent somnolence, fatigue, sedation, and dizziness. Severity and complexity of sexual symptoms had no bearing on success, nor, apparently, did race or Hispanic ethnicity. Associations of HSDD with androgen abnormalities have been inconsistent. Disparities between studies might be rationalized as 3 androgenically distinct forms of HSDD: normo-androgenic, low-androgen, and androgen-insensitivity HSDD. Normo-androgenic appears to be psychosocially rather than biologically driven. Low-androgen appears more frequent in women in or after the menopausal transition (T-responsive). Androgen-insensitive HSDD was found in the majority of premenopausal women in a recent small study. Androgenically distinct forms of HSDD might require different treatments. Low-androgen HSDD was associated with less response to FLI, as was (androgen-suppressing) HC use. Thus, FLI, acting as a serotonergic agent to undo dysfunctional over-activation of sexual inhibition, appears to be most valuable for normo-androgenic HSDD; T treatment, most valuable for low-androgen HSDD. Androgen-insensitive HSDD might require bypassing the androgenic, desire-enhancing influences on dopamine and instead promoting central dopaminergic function more directly.