Sexual Desire vs Arousal
Sexual desire is the motivational interest in sexual activity while arousal is the genital and subjective response to stimulation, and the two dissociate enough that trials measure them separately.
Desire and arousal are separate constructs with separate physiology. Desire is motivational, a spontaneous or responsive interest mediated through central dopaminergic, melanocortin and serotonergic circuits. Arousal is a response: genital vasocongestion driven by nitric oxide and autonomic outflow, plus the subjective sense of being aroused. A drug can move one without touching the other, which is why phosphodiesterase inhibitors improve erectile response and leave low desire untouched.
The two drugs approved for hypoactive sexual desire disorder in premenopausal women both act centrally. Flibanserin, approved in 2015, is a daily oral serotonin receptor agent carrying an alcohol-related hypotension and syncope warning; bremelanotide, approved in 2019, is an on-demand subcutaneous melanocortin agonist causing nausea in a large minority. Both cleared regulatory thresholds on small average gains, roughly half to one extra satisfying sexual event per month over placebo.
That gap between statistical significance and felt benefit is the field's central difficulty. The endpoints are questionnaire-based - desire domain scores, distress scales, event counts - and none is physiological, so placebo response is large and effect sizes stay modest. Distress is part of the diagnosis rather than an add-on: low desire without distress is not a disorder, which is why trials enrol against both criteria.
The measurement error worth knowing is treating genital response as evidence of desire. Concordance between measured genital arousal and reported desire is low, particularly in women, so a physiological readout can rise while interest does not. Marketing for unapproved melanocortin peptides exploits that conflation, describing an erectile or lubrication effect as if it demonstrated restored libido - precisely the inference the approved trials were designed not to make.