Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder : A Randomized Clinical Trial
Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior.
Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD.
Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021.
Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo.
Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal.
Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02).
Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire.
Trial Registration: isrctn.org Identifier: ISRCTN17271094.
| Errataetall: |
CommentIn: MMW Fortschr Med. 2023 Mar;165(4):10. - PMID 36826636 |
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| Medienart: |
E-Artikel |
| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:6 |
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| Enthalten in: |
JAMA network open - 6(2023), 2 vom: 01. Feb., Seite e2254313 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Mills, Edouard G [VerfasserIn] |
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| Links: |
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| Themen: |
Journal Article |
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| Anmerkungen: |
Date Completed 07.02.2023 Date Revised 28.02.2023 published: Electronic ISRCTN: ISRCTN17271094 CommentIn: MMW Fortschr Med. 2023 Mar;165(4):10. - PMID 36826636 Citation Status MEDLINE |
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| doi: |
10.1001/jamanetworkopen.2022.54313 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
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| 100 | 1 | |a Mills, Edouard G |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effects of Kisspeptin on Sexual Brain Processing and Penile Tumescence in Men With Hypoactive Sexual Desire Disorder |b A Randomized Clinical Trial |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 07.02.2023 | ||
| 500 | |a Date Revised 28.02.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a ISRCTN: ISRCTN17271094 | ||
| 500 | |a CommentIn: MMW Fortschr Med. 2023 Mar;165(4):10. - PMID 36826636 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Importance: The human physiological sexual response is crucial for reward, satisfaction, and reproduction. Disruption of the associated neurophysiological pathways predisposes to low sexual desire; the most prevalent psychological form is hypoactive sexual desire disorder (HSDD), which affects 8% of men but currently has no effective pharmacological treatment options. The reproductive neuropeptide kisspeptin offers a putative therapeutic target, owing to emerging understanding of its role in reproductive behavior | ||
| 520 | |a Objective: To determine the physiological, behavioral, neural, and hormonal effects of kisspeptin administration in men with HSDD | ||
| 520 | |a Design, Setting, and Participants: This double-blind, 2-way crossover, placebo-controlled randomized clinical trial was performed at a single academic research center in the UK. Eligible participants were right-handed heterosexual men with HSDD. Physiological, behavioral, functional magnetic resonance imaging (fMRI), and hormonal analyses were used to investigate the clinical and mechanistic effects of kisspeptin administration in response to visual sexual stimuli (short and long video tasks). The trial was conducted between January 11 and September 15, 2021, and data analysis was performed between October and November 2021 | ||
| 520 | |a Interventions: Participants attended 2 study visits at least 7 days apart, in balanced random order, for intravenous infusion of kisspeptin-54 (1 nmol/kg/h) for 75 minutes or for administration of a rate-matched placebo | ||
| 520 | |a Main Outcomes and Measures: Changes in (1) brain activity on whole-brain analysis, as determined by fMRI blood oxygen level-dependent activity in response to visual sexual stimuli during kisspeptin administration compared with placebo, (2) physiological sexual arousal (penile tumescence), and (3) behavioral measures of sexual desire and arousal | ||
| 520 | |a Results: Of the 37 men randomized, 32 completed the trial. Participants had a mean (SD) age of 37.9 (8.6) years and a mean (SD) body mass index of 24.9 (5.4). On viewing sexual videos, kisspeptin significantly modulated brain activity in key structures of the sexual-processing network on whole-brain analysis compared with placebo (mean absolute change [Cohen d] = 0.81 [95% CI, 0.41-1.21]; P = .003). Furthermore, improvements in several secondary analyses were observed, including significant increases in penile tumescence in response to sexual stimuli (by up to 56% more than placebo; mean difference = 0.28 units [95% CI, 0.04-0.52 units]; P = .02) and behavioral measures of sexual desire-most notably, increased happiness about sex (mean difference = 0.63 points [95% CI, 0.10-1.15 points]; P = .02) | ||
| 520 | |a Conclusions and Relevance: Collectively, this randomized clinical trial provides the first evidence to date showing that kisspeptin administration substantially modulates sexual brain processing in men with HSDD, with associated increases in penile tumescence and behavioral measures of sexual desire and arousal. These data suggest that kisspeptin has potential as the first pharmacological treatment for men with low sexual desire | ||
| 520 | |a Trial Registration: isrctn.org Identifier: ISRCTN17271094 | ||
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Kisspeptins |2 NLM | |
| 700 | 1 | |a Ertl, Natalie |e verfasserin |4 aut | |
| 700 | 1 | |a Wall, Matthew B |e verfasserin |4 aut | |
| 700 | 1 | |a Thurston, Layla |e verfasserin |4 aut | |
| 700 | 1 | |a Yang, Lisa |e verfasserin |4 aut | |
| 700 | 1 | |a Suladze, Sofiya |e verfasserin |4 aut | |
| 700 | 1 | |a Hunjan, Tia |e verfasserin |4 aut | |
| 700 | 1 | |a Phylactou, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Bijal |e verfasserin |4 aut | |
| 700 | 1 | |a Muzi, Beatrice |e verfasserin |4 aut | |
| 700 | 1 | |a Ettehad, Dena |e verfasserin |4 aut | |
| 700 | 1 | |a Bassett, Paul A |e verfasserin |4 aut | |
| 700 | 1 | |a Howard, Jonathan |e verfasserin |4 aut | |
| 700 | 1 | |a Rabiner, Eugenii A |e verfasserin |4 aut | |
| 700 | 1 | |a Bech, Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Abbara, Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Goldmeier, David |e verfasserin |4 aut | |
| 700 | 1 | |a Comninos, Alexander N |e verfasserin |4 aut | |
| 700 | 1 | |a Dhillo, Waljit S |e verfasserin |4 aut | |
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