Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder and Treatment Options

J Sex Med. 2017 Dec;14(12):1575-1584. doi: 10.1016/j.jsxm.2017.10.068.


Background: The neurobiology of sexual response is driven in part by dopamine and serotonin-the former modulating excitatory pathways and the latter regulating inhibitory pathways. Neurobiological underpinnings of hypoactive sexual desire disorder (HSDD) are seemingly related to overactive serotonin activity that results in underactive dopamine activity. As such, pharmacologic agents that decrease serotonin, increase dopamine, or some combination thereof, have therapeutic potential for HSDD.

Aim: To review the role of serotonin in female sexual function and the effects of pharmacologic interventions that target the serotonin system in the treatment of HSDD.

Methods: Searches of the Medline database for articles on serotonin and female sexual function.

Outcomes: Relevant articles from the peer-reviewed literature were included.

Results: Female sexual response is regulated not only by the sex hormones but also by several neurotransmitters. It is postulated that dopamine, norepinephrine, oxytocin, and melanocortins serve as key neuromodulators for the excitatory pathways, whereas serotonin, opioids, and endocannabinoids serve as key neuromodulators for the inhibitory pathways. Serotonin appears to be a key inhibitory modulator of sexual desire, because it decreases the ability of excitatory systems to be activated by sexual cues. Centrally acting drugs that modulate the excitatory and inhibitory pathways involved in sexual desire (eg, bremelanotide, bupropion, buspirone, flibanserin) have been investigated as treatment options for HSDD. However, only flibanserin, a multifunctional serotonin agonist and antagonist (5-hydroxytryptamine [5-HT]1A receptor agonist and 5-HT2A receptor antagonist), is currently approved for the treatment of HSDD.

Clinical implications: The central serotonin system is 1 biochemical target for medications intended to treat HSDD.

Strengths and limitations: This narrative review integrates findings from preclinical studies and clinical trials to elucidate neurobiological underpinnings of HSDD but is limited to 1 neurotransmitter system (serotonin).

Conclusion: Serotonin overactivity is a putative cause of sexual dysfunction in patients with HSDD. The unique pharmacologic profile of flibanserin tones down inhibitory serotonergic function and restores dopaminergic and noradrenergic function. Croft HA. Understanding the Role of Serotonin in Female Hypoactive Sexual Desire Disorder and Treatment Options. J Sex Med 2017;14:1575-1584.

Keywords: Female Sexual Dysfunction; Flibanserin; Hypoactive Sexual Desire Disorder; Serotonin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dopamine / metabolism
  • Female
  • Humans
  • Male
  • Receptor, Serotonin, 5-HT2A / metabolism
  • Serotonin / metabolism*
  • Serotonin 5-HT2 Receptor Antagonists / administration & dosage
  • Serotonin Receptor Agonists / administration & dosage
  • Sexual Behavior
  • Sexual Dysfunctions, Psychological / drug therapy
  • Sexual Dysfunctions, Psychological / metabolism*
  • Sexual Dysfunctions, Psychological / psychology


  • Receptor, Serotonin, 5-HT2A
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin Receptor Agonists
  • Serotonin
  • Dopamine