2026 ECNP Congress

PS01-1063

Striatal serotonin 4 receptor binding and female sexual desire: cross sectional positron emission tomography results

Annika Fuglsang-Damgaard — A. Giraldi, S.V. Larsen, V.G. Frokjaer · Copenhagen University Hospital - Rigshospitalet, Neurobiology Research Unit, Copenhagen, Denmark

2026 ECNP Congress

Introduction

Compromised sexual function and sexual desire may have many origins, but a possible mechanism involves the serotonin 4 receptor (5-HT4R). The 5-HT4R is densely expressed in the striatum, a key reward-region, and is relevant in both depressed and non-depressed states. Reduced striatal 5-HT4R availability or activity may impair reward processing, contributing to anhedonia (i.e., lack of interest in what is usually pleasurable), including lower sexual desire. Consistent with this, our group has found that unmedicated women with depression and scores indicative of sexual dysfunction have lower striatal 5-HT4R binding versus unmedicated depressed women without sexual dysfunction. Moreover, we found a positive correlation between striatal 5-HT4R and the degree of experienced sexual desire [1]. A relevant factor to consider is the influence of hormonal contraceptives, as use of combined oral contraceptives is associated with reduced 5-HT4R binding [2] and has been linked to low sexual desire [3].

Aims

In this study, whether striatal 5-HT4R binding is associated with sexual desire and overall sexual function in healthy women, and whether this association depends on hormonal contraceptive use.

Methods

This cross-sectional study is made available from the Centre for Integrated Molecular Brain Imaging (CIMBI) database [4]. Sexual desire is measured with the sexual desire/interest subscale of the Changes in Sexual Functioning Questionnaire (CSFQ-14). Overall sexual function is dichotomized as either being in risk of having sexual dysfunction or not based on validated cut-off points from the CSFQ-14 total score. Striatal 5-HT4R binding is quantified with positron emission tomography (PET) using the radiotracer [11C]-SB207145. We included healthy participants who completed the CSFQ‑14 within four weeks of their PET scan and excluded those without reliable contraception information, yielding a final sample of 62 participants. We tested the associations between sexual measures (i.e. sexual desire and dichotomized sexual function) and striatal 5-HT4R binding using multiple linear regression models adjusted for age and injected tracer dose per kg bodyweight, including an interaction term for hormonal contraceptive use. Hormonal contraception was stratified in three: natural cycling (n=51), combined oral contraceptives (n=5) and hormonal intrauterine device (n=6). The analysis plan was preregistered on aspredicted.org (#275259).

Results

We found no evidence for an association between sexual desire and striatal 5-HT4R (β = -0.02, 95% CI [-0.07, 0.03], p = 0.48). However, interaction analysis suggested a trend towards a crossover interaction between natural cycling women and hormonal IUD users in the association between sexual desire and striatal 5-HT4R (β = -0.23, 95% CI [-0.49, 0.02], p = 0.071). There was no association between dichotomized sexual function and striatal 5-HT4R (β = -0.16, 95% CI [-0.44, 0.12], p = 0.26).

Conclusions

In this sample of healthy women, striatal 5-HT4R binding was not associated with sexual desire or overall sexual function. Sample size limits conclusions about the moderating role of hormonal contraceptives, but results underscore the importance of considering contraceptive use in future studies.

References

  1. Rasmussen, A. L., Larsen, S. V., Ozenne, B., Köhler-Forsberg, K., Stenbæk, D. S., Jørgensen, M. B., Giraldi, A., & Frokjaer, V. G. (2023). Sexual health and serotonin 4 receptor brain binding in unmedicated patients with depression-a NeuroPharm study. Translational Psychiatry, 13(1), Article 247. https://doi.org/10.1038/s41398- 023-02551-x
  2. Larsen, S. V. et al. Oral contraceptives and the serotonin 4 receptor: a molecular brain imaging study in healthy women. Acta Psychiatr. Scand. 142, 294–306 (2020).
  3. Lundin, C. et al. Sexual function and combined oral contraceptives: A randomized placebo-controlled trial. Endocr. Connect. 7, 1208–1216 (2018)
  4. Knudsen, G.M., Jensen, P.S., Erritzoe, D., Baaré, W.F.C., Ettrup, A., Fisher, P.M., Gillings, N., Hansen, H.D., Hansen, L.K., Hasselbalch, S.G., Henningsson, S., Herth, M.M., Holst, K.K., Iversen, P., Kessing, L.V., Macoveanu, J., Madsen, K.S., Mortensen, E.L., Nielsen, F.Å., Paulson, O.B., Siebner, H.R., Stenbæk, D.S., Svarer, C., Jernigan, T.L., Strother, S.C., Frokjaer, V.G., 2016. The Center for Integrated Molecular Brain Imaging (Cimbi) database. NeuroImage 124, 1213–1219. doi:10.1016/j.neuroimage.2015.04.025