Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case‐Controlled Study
Objective Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear. Methods We performed a prospective, case‐controlled study in adult males with cluste...
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| Veröffentlicht in: | Annals of neurology 2024-06, Vol.95 (6), p.1149-1161 |
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| container_title | Annals of neurology |
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| creator | Petersen, Anja S. Kristensen, David M. Westgate, Connar S. J. Folkmann‐Hansen, Thomas Lund, Nunu Barloese, Mads Søborg, Marie‐Louise K. Snoer, Agneta Johannsen, Trine H. Frederiksen, Hanne Juul, Anders Jensen, Rigmor H. |
| description | Objective
Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
Methods
We performed a prospective, case‐controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone‐binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age‐ and sex‐matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
Results
The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%–47%, p |
| doi_str_mv | 10.1002/ana.26906 |
| format | Article |
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Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
Methods
We performed a prospective, case‐controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone‐binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age‐ and sex‐matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
Results
The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%–47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%–37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified.
Interpretation
Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149–1161</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.26906</identifier><identifier>PMID: 38558306</identifier><language>eng</language><publisher>Hoboken, USA: John Wiley & Sons, Inc</publisher><subject>Adult ; Alleles ; Androgens ; Case-Control Studies ; Chromosome 17 ; Cluster Headache - blood ; Cluster Headache - genetics ; Clusters ; Endocrine system ; Globulins ; Headache ; Headaches ; Hormones ; Humans ; Hypogonadism ; Hypogonadism - blood ; Hypogonadism - genetics ; Luteinizing hormone ; Luteinizing Hormone - blood ; Male ; Males ; Middle Aged ; Prospective Studies ; Remission ; Sex Hormone-Binding Globulin - genetics ; Sex hormones ; Sleep ; Tau protein ; Testosterone ; Testosterone - blood</subject><ispartof>Annals of neurology, 2024-06, Vol.95 (6), p.1149-1161</ispartof><rights>2024 The Authors. published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2024 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.</rights><rights>2024. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3886-8381f9cdd3df94c1cea24572f0e82c0dbe765cff2d196162e1d1dae26110dca3</citedby><cites>FETCH-LOGICAL-c3886-8381f9cdd3df94c1cea24572f0e82c0dbe765cff2d196162e1d1dae26110dca3</cites><orcidid>0000-0002-0125-6038 ; 0000-0001-6703-7762 ; 0000-0001-5066-8306</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.26906$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.26906$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38558306$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Petersen, Anja S.</creatorcontrib><creatorcontrib>Kristensen, David M.</creatorcontrib><creatorcontrib>Westgate, Connar S. J.</creatorcontrib><creatorcontrib>Folkmann‐Hansen, Thomas</creatorcontrib><creatorcontrib>Lund, Nunu</creatorcontrib><creatorcontrib>Barloese, Mads</creatorcontrib><creatorcontrib>Søborg, Marie‐Louise K.</creatorcontrib><creatorcontrib>Snoer, Agneta</creatorcontrib><creatorcontrib>Johannsen, Trine H.</creatorcontrib><creatorcontrib>Frederiksen, Hanne</creatorcontrib><creatorcontrib>Juul, Anders</creatorcontrib><creatorcontrib>Jensen, Rigmor H.</creatorcontrib><title>Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case‐Controlled Study</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
Methods
We performed a prospective, case‐controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone‐binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age‐ and sex‐matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
Results
The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%–47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%–37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified.
Interpretation
Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149–1161</description><subject>Adult</subject><subject>Alleles</subject><subject>Androgens</subject><subject>Case-Control Studies</subject><subject>Chromosome 17</subject><subject>Cluster Headache - blood</subject><subject>Cluster Headache - genetics</subject><subject>Clusters</subject><subject>Endocrine system</subject><subject>Globulins</subject><subject>Headache</subject><subject>Headaches</subject><subject>Hormones</subject><subject>Humans</subject><subject>Hypogonadism</subject><subject>Hypogonadism - blood</subject><subject>Hypogonadism - genetics</subject><subject>Luteinizing hormone</subject><subject>Luteinizing Hormone - blood</subject><subject>Male</subject><subject>Males</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Remission</subject><subject>Sex Hormone-Binding Globulin - genetics</subject><subject>Sex hormones</subject><subject>Sleep</subject><subject>Tau protein</subject><subject>Testosterone</subject><subject>Testosterone - blood</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kMtOwzAQRS0EglJY8APIEhtYpPiRuA67KgJaiZcE-8jYE3CVxCFOqLrjE_hGvgSXAgskViONzlzNPQgdUDKihLBTVasREykRG2hAE04jyeJ0Ew0IF3GUUB7voF3v54SQVFCyjXa4TBLJiRggm7mqgdqrDgyeLhv35GplrK_wzEDd2cKGva3xtSrB44XtnnFW9r6DFk9BGaWf4QxP8F3rfAO6s6-AM-Xh4-09c3XXurIM9_ddb5Z7aKtQpYf97zlEDxfnD9k0urq9nGWTq0hzKUUkuaRFqo3hpkhjTTUoFidjVhCQTBPzCGOR6KJghoYyggE11ChgglJitOJDdLyObVr30oPv8sp6DWWpanC9zznhlHImhQjo0R907vq2Ds8FKghKgqEVdbKmdOjoWyjyprWVapc5JflKfx7051_6A3v4ndg_VmB-yR_fAThdAwtbwvL_pHxyM1lHfgJWmI_M</recordid><startdate>202406</startdate><enddate>202406</enddate><creator>Petersen, Anja S.</creator><creator>Kristensen, David M.</creator><creator>Westgate, Connar S. J.</creator><creator>Folkmann‐Hansen, Thomas</creator><creator>Lund, Nunu</creator><creator>Barloese, Mads</creator><creator>Søborg, Marie‐Louise K.</creator><creator>Snoer, Agneta</creator><creator>Johannsen, Trine H.</creator><creator>Frederiksen, Hanne</creator><creator>Juul, Anders</creator><creator>Jensen, Rigmor H.</creator><general>John Wiley & Sons, Inc</general><general>Wiley Subscription Services, Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0002-0125-6038</orcidid><orcidid>https://orcid.org/0000-0001-6703-7762</orcidid><orcidid>https://orcid.org/0000-0001-5066-8306</orcidid></search><sort><creationdate>202406</creationdate><title>Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case‐Controlled Study</title><author>Petersen, Anja S. ; Kristensen, David M. ; Westgate, Connar S. J. ; Folkmann‐Hansen, Thomas ; Lund, Nunu ; Barloese, Mads ; Søborg, Marie‐Louise K. ; Snoer, Agneta ; Johannsen, Trine H. ; Frederiksen, Hanne ; Juul, Anders ; Jensen, Rigmor H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3886-8381f9cdd3df94c1cea24572f0e82c0dbe765cff2d196162e1d1dae26110dca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adult</topic><topic>Alleles</topic><topic>Androgens</topic><topic>Case-Control Studies</topic><topic>Chromosome 17</topic><topic>Cluster Headache - blood</topic><topic>Cluster Headache - genetics</topic><topic>Clusters</topic><topic>Endocrine system</topic><topic>Globulins</topic><topic>Headache</topic><topic>Headaches</topic><topic>Hormones</topic><topic>Humans</topic><topic>Hypogonadism</topic><topic>Hypogonadism - blood</topic><topic>Hypogonadism - genetics</topic><topic>Luteinizing hormone</topic><topic>Luteinizing Hormone - blood</topic><topic>Male</topic><topic>Males</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Remission</topic><topic>Sex Hormone-Binding Globulin - genetics</topic><topic>Sex hormones</topic><topic>Sleep</topic><topic>Tau protein</topic><topic>Testosterone</topic><topic>Testosterone - blood</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Petersen, Anja S.</creatorcontrib><creatorcontrib>Kristensen, David M.</creatorcontrib><creatorcontrib>Westgate, Connar S. J.</creatorcontrib><creatorcontrib>Folkmann‐Hansen, Thomas</creatorcontrib><creatorcontrib>Lund, Nunu</creatorcontrib><creatorcontrib>Barloese, Mads</creatorcontrib><creatorcontrib>Søborg, Marie‐Louise K.</creatorcontrib><creatorcontrib>Snoer, Agneta</creatorcontrib><creatorcontrib>Johannsen, Trine H.</creatorcontrib><creatorcontrib>Frederiksen, Hanne</creatorcontrib><creatorcontrib>Juul, Anders</creatorcontrib><creatorcontrib>Jensen, Rigmor H.</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Petersen, Anja S.</au><au>Kristensen, David M.</au><au>Westgate, Connar S. J.</au><au>Folkmann‐Hansen, Thomas</au><au>Lund, Nunu</au><au>Barloese, Mads</au><au>Søborg, Marie‐Louise K.</au><au>Snoer, Agneta</au><au>Johannsen, Trine H.</au><au>Frederiksen, Hanne</au><au>Juul, Anders</au><au>Jensen, Rigmor H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case‐Controlled Study</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2024-06</date><risdate>2024</risdate><volume>95</volume><issue>6</issue><spage>1149</spage><epage>1161</epage><pages>1149-1161</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><abstract>Objective
Androgens have been hypothesized to be involved in the pathophysiology of cluster headache due to the male predominance, but whether androgens are altered in patients with cluster headache remains unclear.
Methods
We performed a prospective, case‐controlled study in adult males with cluster headache. Sera were measured for hormones including testosterone, luteinizing hormone (LH), and sex hormone‐binding globulin in 60 participants with episodic cluster headache (during a bout and in remission), 60 participants with chronic cluster headache, and 60 age‐ and sex‐matched healthy controls. Free testosterone (fT) was calculated according to the Vermeulen equation. Shared genetic risk variants were assessed between cluster headache and testosterone concentrations.
Results
The mean fT/LH ratio was reduced by 35% (95% confidence interval [CI]: 21%–47%, p < 0.0001) in patients with chronic cluster headache and by 24% (95% CI: 9%–37%, p = 0.004) in patients with episodic cluster headache compared to controls after adjusting for age, sleep duration, and use of acute medication. Androgen concentrations did not differ between bouts and remissions. Furthermore, a shared genetic risk allele, rs112572874 (located in the intron of the microtubule associated protein tau (MAPT) gene on chromosome 17), between fT and cluster headache was identified.
Interpretation
Our results demonstrate that the male endocrine system is altered in patients with cluster headache to a state of compensated hypogonadism, and this is not an epiphenomenon associated with sleep or the use of acute medication. Together with the identified shared genetic risk allele, this may suggest a pathophysiological link between cluster headache and fT. ANN NEUROL 2024;95:1149–1161</abstract><cop>Hoboken, USA</cop><pub>John Wiley & Sons, Inc</pub><pmid>38558306</pmid><doi>10.1002/ana.26906</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0002-0125-6038</orcidid><orcidid>https://orcid.org/0000-0001-6703-7762</orcidid><orcidid>https://orcid.org/0000-0001-5066-8306</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Adult Alleles Androgens Case-Control Studies Chromosome 17 Cluster Headache - blood Cluster Headache - genetics Clusters Endocrine system Globulins Headache Headaches Hormones Humans Hypogonadism Hypogonadism - blood Hypogonadism - genetics Luteinizing hormone Luteinizing Hormone - blood Male Males Middle Aged Prospective Studies Remission Sex Hormone-Binding Globulin - genetics Sex hormones Sleep Tau protein Testosterone Testosterone - blood |
| title | Compensated Hypogonadism Identified in Males with Cluster Headache: A Prospective Case‐Controlled Study |
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